The objective of this work is to determine the mode of action of helper T cells in the induction of antibody synthesis. Spleen cells have been stimulated with Concanavalin A (Con A) under conditions which lead to the production of TRF in the culture supernatants from single T cells. These supernatants have been assayed in multiple microcultures of B cells containing two heterologous erthrocyte antigens. When produced in conditions of limiting dilution, the TRF show a segregaton of biologic activities as revealed by an ability to stimulate immune responses to one erythrocyte but not another. These results indicate that TRF produced in Con A-treated spleen cultures have antigenic specificity. We postulate these culture supernatants derived from Con-A-activated spleen cells contain receptors derived from helper T cells, and that all T cell-replacing activity observed is due to the expression of the biologic activity of these receptors. Con A-treated spleen cells produce a polyclonal mixture of T cell receptors, hence the culture supernatants are apparently antigen non-specific. The I-region of antibody responses to soluble calf skin collagen has been examined. We plan to determine whether any component of TRF shows specificity in binding to collagen, and the relationship of TRF to I-region gene products.